•
Finish – Autonomic nervous system
•
Start – hormones and endocrinology
1. Pituitary gland
2. Adrenal glands
Muscarinic Ach
receptors
Parasympathetic
Nictonic Ach receptors
Sympathetic
α or β adrenergic
receptors
Receptor Types
Sympathetic
Transmitter of
Preganglionic
Neuron
Receptors on
Postganglionic
Neuron
Transmitter of
Postganglionic
Neuron
Receptors on
target tissue
Acetylcholine
(Ach)
Nicotinic Ach
receptors
Norepinephrine
(noradrenaline)
α or β
adrenergic
receptors
Nicotinic Ach receptor
Ligand-gated ion channel
Parasympathetic
Ach
Nicotinic Ach
receptors
Ach
Muscarinic Ach receptor
α and β adrenergic receptors
G-protein coupled receptors
Muscarinic Ach
receptors
Subtypes of adrenergic
receptors:
α1, α2 and β1, β2
1
Effector
SNS
receptor
Sympathetic
effect
Parasymp
effect
Eye
α1
opens pupil
closes pupil
Heart
β1
↑HR
↓HR
Atria
β1, β2
↑ contractility
↓ contractility
AV node
β1, β2
↑ conduction
↓ conduction
Ventricles
β1, β2
↑ contractility
↓ contractility
α1, α2
Constricts
--
α1
constricts
--
β2
dilates
--
α1
constricts
--
β2
dilates
--
α1, α2
constricts
--
β2
dilates
--
β2
Relaxes
Constricts
SA node
Arterioles in the:
Skin
Muscle
organs
Veins
Table 6-11
Lung bronchial
muscle
Hormones
• Robert Wadlow
– 8’-11” tall
– 496 pounds
– Size 37 shoe
• Too much growth
hormone
Pharmacology of Autonomic
Nervous System
• Many Drugs target either SNS or PNS
– Asthma - β agonist (activator)
– Blood Pressure - β blocker
– Nicotine!
Hormones
Topics:
• Types of hormones
• Signal transduction pathways
• Major Hormone systems
• Hormonal control of physiological
processes
2
Hormones
Mechanisms of Secretion
Ca++
•
•
Another form of communication
Neuron
Types of Secretion
1.
2.
3.
4.
Autocrine – affects the secreting cell
Paracrine – affects neighbouring cell
Endocrine – secreted into bloodstream
Exocrine – secreted onto body surface,
including surface of gut
Ca++
Neurosecretory cell
Ca++
Capillary
Simple Endocrine Cell
Ca++
Intracellular Ca stores
• Secretory Pathway in Endocrine cells
Exocytosis
• Neurosecretory cells
Ca++
– Work like all neurons
Secretory vesicle
Like synaptic vesicle
secretion, these
steps also require
SNARE proteins
Sensory Input → APs → secretion
– Except secrete into bloodstream
Golgi
Rough ER
Nucleus
3
Two types of hormones
Two types of hormones
1. Lipid-soluble
Carrier molecule
• Lipid Soluble
Hormone molecule
– Steroid hormones (eg cortisol, estrogen, testosterone)
– Thyroid hormones
• Lipid Insoluble
Cytoplasmic receptor
– Peptides and Proteins (eg insulin, ACTH)
– Catecholamines (eg adrenalin)
Nuclear receptor
Transcription &
Translation
long lasting effects
Two types of hormones
2. Lipid-insoluble
Nucleus
Signal Transduction
Signal
Hormone molecule
Plasma membrane receptor
Reception, Transduction
Second Messengers
Second Messenger
Regulators
Specific Effectors
Effector Protein
Cellular Response
Cellular effects
4
1 molecule
Types of Second Messengers
1. Cyclic nucleotides
– cAMP, cGMP
2. Inositol phospholipid
amplification
– Inositol 1,4,5 triphosphate (IP3)
– 1,2-diacylglycerol (DAG)
3. Calcium ions (Ca++)
10,000 molecules
cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate
Cyclase
Gs
Gi
stimulates
ATP
cAMP / Protein Kinase A Pathway
Ri
Rs
inhibits
Adenylate
Cyclase
Gs
ATP
cAMP
Protein Kinase A
Gi
cAMP
Regulatory subunit
Protein Kinase A
Catalytic subunit
Ion
Channels
Membrane
Pumps
Metabolic
Enzymes
Effects
5
Inositol Phospholipid Pathway
Phospholipase C
Phosphatidylserine
DAG
PIP2
Protein Kinase C
G-protein
IP3
Ca++
Cellular Response
Intracellular Ca++
stores
1. Receptor / G-protein activate
phospholipase C
2. PLC catalyzes PIP2 → IP3 and DAG
3. IP3 → release of Ca++ from intracellular
stores (ER)
4. DAG (together with Ca++ and PS)
activate Protein Kinase C
Phosphatidylserine
Other Ca++
Dependent processes
Calcium as second messenger
Ca++
Guanylate cyclase
Pituitary gland
• Master gland
– Secretes 9 hormones that control other
glands
• 2 distinct parts
GTP
cGMP
Protein Kinase G
Ca++
Intracellular Ca++
stores
Protein Kinase C
Cam Kinase II
Calcium / Calmodulin
Adenylate
cyclase
– Anterior pituitary (adenohypophysis)
– Posterior pituitary (neurohypophysis)
• Both parts controlled by neurosecretory
cells of the hypothalamus (part of the
brain!)
Metabolic
Enzymes
6
Neurosecretory
neurons
Pituitary
Anterior Pituitary
Posterior Pituitary
Anterior Pituitary
• Neurosecretory neurons → Anterior Pituitary
– Secrete hormones onto median eminence and
transported to Ant Pit by portal blood vessels
– Regulate secretion of other hormones from anterior
pituitary cells
• Neurosecretory neurons → Posterior Pituitary
Multi-hormone system
– 1st hormone stimulates or inhibits release of
other hormones from anterior pituitary
– 2nd hormone has effect on target tissue
– Sometimes the effect is to release a 3rd
hormone from the target tissue
– Secrete hormones directly into capillaries
7
1st hormone
2nd hormone
– GnRH – Gonadotropin releasing
hormone
– GHRH - Growth Hormone
Releasing Hormone
– SS - Somatostatin
– Thyroid hormone releasing
hormone (TRH)
– Corticotropin-releasing hormone
(CRH)
– Prolactin-inhibiting
hormone/dopamine (PIH/DA)
Hypothalamus
– FSH/LH – Follicle
Stimulating Hormone / LH
Luteinizing Hormone
GnRh
GHRH
SS
FSH &
LH
Growth
Hormone
– GH – Growth Hormone
– TSH - Thyroid stimulating
hormone
– ACTH -Adrenocorticotropin
hormone
– Prolactin
TRH
PIH/DA
CRH
Prolactin
ACTH
Anterior Pituitary
Gonads
TSH
Many tissues
Thyroid Breasts
Adrenal Cortex
Germ cell development
Secrete Hormones
•Estrogen, Progesterone
•Testosterone
Inhibits secretion
Control of Anterior Pituitary
Protein synthesis
Metabolism
Secrete thyroid
hormones
Development &
Milk production
Secrete Cortisol
stimulates secretion
Posterior Pituitary
Neural stimulus
Hypothalmic Neurosecretory cells
Negative feedback
•
Releasing and release-inhibiting hormones
•
Anterior pituitary gland
Growth hormone
prolactin
Non-endocrine Tissue
Metabolic response
ACTH
TSH
FSH / LH
Endocrine Tissue
Neurosecretory cells secrete hormones
directly onto capillaries
Only 2 hormones:
1. Antidiuretic hormone (ADH, also called
vasopressin)
•
Water retention by the kidney
2. Oxytocin
•
•
Uterine contractions during childbirth
Milk ejection during breast feeding
hormone
8
The Adrenal Glands
• An example of Pituitary control over other
endocrine tissue
• One gland attached to the top of each
kidney
Functional Anatomy of Adrenal Glands
Hormone
Zona
glomerulosa
Cortex
Adrenal Medulla
Zona
fasciculata
Cortisol and
Testosterone, progesterone
Zona
reticularis
Adrenal Cortex
Medulla
Fig 9-32
aldosterone
Epinephrine &
norepinephrine
Kidney
Cortex
Medulla
Adrenal Cortical Steroids
Adrenal Cortex
• Steroid hormones
– Aldosterone
– Cortisol
– Small amounts of
testosterone,
progesterone
Adrenal Medulla
• Catecholamine
– Epinipherine (adrenalin)
– Norepinipherine
(noradrenalin)
• Mineralocorticoids
– eg. aldosterone
– Controls ion transport
in the kidney function
– Regulates expression
of a Na channel
– Important for water
reabsorption
• Glucocorticoids
– eg. cortisol
– Important for
metabolism esp. glucose
– Activate enzymes (in
liver) that increase
glucose production
– ↑ blood glucose
9
Control of Adrenal Cortex
Stress, circadian rhythm
and other neural input
Hypothalamic neurons
Corticotropin releasing hormone (CRH)
What is the effect of ACTH on the
adrenal cortical cells?
• Leads to the production and secretion of
depolarization
cortisol…..but how?
Rs
Adenylate
Cyclase
Gs
Anterior Pituitary
Adrenocorticotropic hormone (ACTH)
K+ channel
ATP
Ca++
cAMP
2
Protein Kinase A
Adrenal cortex
1
Release of steroid hormones
Activate enzymes
Req’d for cortisol production
↑ cortisol
What are the effects of cortisol?
1. Energy Mobilization:
a. ↑ glucose production by liver
b. ↑ protein breakdown in muscle
c. ↑ fatty acids in blood
2. Permissiveness
• Recall cortisol is a lipid-soluble hormone
– Nuclear receptor activates transcription
– e.g. cortisol ↑ tyrosine aminotransferase
transcription, an enzyme important for
glucose production in the liver
a. Most other hormones work better in the
presence of cortisol
3. Anti-inflammatory
10
Adrenal Gland Part 2
Adrenal Medulla
Hormone
Zona
glomerulosa
Cortex
Adrenal Gland Part 2
Adrenal Medulla
aldosterone
Zona
fasciculata
Cortisol and
Testosterone, progesterone
Zona
reticularis
Medulla
• Catecholamines stored in large vesicles within
chromaffin cells of the adrenal medulla
• Chromaffin cells innervated by neurons of the
sympathetic nervous system
• ‘Fight or flight’ response
Epinephrine &
norepinephrine
Cortex
Medulla
Sympathetic nerve terminal
Acetycholine synapse
Ca++
Adrenal medulla
Catecholamine
containing vesicles
Chromaffin cell
• Ach depolarizes chromaffin cell by
activating nicotinic Ach receptors
• Opens voltage-gated Ca++ channels
• Ca++ causes fusion of vesicles
• Release of catecholamine into blood
stream
Epi
NE
Blood vessel
11
Effects of catecholamines depend
upon receptor type
• Catecholamines released by adrenal
medulla:
• Activate adrenergic receptors
– Two types: α and β
– 80% epinipherine
– 20% norepiniphrine
α1
Recall Norepinephrine is the Sympathetic NS
postganglionic neurotransmitter
activates
α2
β1
β2
Phospholipase C
Adenylate cyclase
IP3 & DAG
cAMP
inhibits
Potential effects of catecholamine
receptor activation
Overall, Epi or NE from adrenal
medulla have similar effects as NE
from SNS activity
• Heart
•
• Smooth Muscle
– β mediated ↑ - contraction, HR
•
•
Effects Epi/NE from adrenal medulla last 5-10X longer
than effects of SNS due to blood circulation
Epi is a little more effective at activating β receptors
than norepi
Epi is more effective at ↑ metabolic rate of all cells
– α contraction (Blood vessels)
– β relaxation (lungs)
• Metabolism
– β - ↑ glycogenolysis → glucose
• Neural
– β - ↓ K+ channel conductance
12
Summary
• Pituitary gland
– Hypothalamic control
– Anterior – 2 hormone system
– Posterior – direct hormone release into blood
stream
• Adrenal gland
– Cortex – steroid hormones
– Medulla - catecholamines
13